Author, as appears in the article.: Wu, Zhenhua; Suppo, Jean-Simon; Tumova, Sarka; Strope, Jonathan; Bravo, Fernando; Moy, Melody; Weinstein, Ethan S.; Peer, Cody J.; Figg, William D.; Chain, William J.; Echavarren, Antonio M.; Beech, David J.; Beutler, John A.;
Department: Química Analítica i Química Orgànica
URV's Author/s: BRAVO LARA, FERNANDO / ECHAVARREN PABLOS, ANTONIO
Keywords: Trpc4 Tonantzitlolone Pkc-theta Mice Kidney cancer Ion channels Formal synthesis Englerin Cytotoxicity Channels Biological evaluation (-)-englerin
Abstract: Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Thematic Areas: Química Organic chemistry Medicina ii Medicina i Materiais Interdisciplinar Farmacia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Chemistry, medicinal Biotecnología Biochemistry
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: antoniomaria.echavarren@urv.cat
Author identifier: 0000-0002-6418-7930
Record's date: 2024-01-14
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00186
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Acs Medicinal Chemistry Letters. 11 (9): 1711-1716
APA: Wu, Zhenhua; Suppo, Jean-Simon; Tumova, Sarka; Strope, Jonathan; Bravo, Fernando; Moy, Melody; Weinstein, Ethan S.; Peer, Cody J.; Figg, William D.; C (2020). Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition. Acs Medicinal Chemistry Letters, 11(9), 1711-1716. DOI: 10.1021/acsmedchemlett.0c00186
Article's DOI: 10.1021/acsmedchemlett.0c00186
Entity: Universitat Rovira i Virgili
Journal publication year: 2020
Publication Type: Journal Publications
Repositori URV